Crystal structure of the acyclic form of 1-de­oxy-1-[(4-methoxyphenyl)(methyl)amino]-d-fructose

The monoclinic unit contains a rare acyclic keto tautomer of the amino sugar involved in the extensive hydrogen-bonding patterns. The acyclic conformation is a minor species in the compound’s solution.

Abstract

The title compound, C₁₄H₂₁NO₆, (I), crystallizes exclusively in the acyclic keto form. In solution of (I), the acyclic tautomer represents only 10% of the population in equilibrium, with the other 90% consisting of β-pyran­ose, β-furan­ose, α-pyran­ose, and α-furan­ose cyclic forms. The carbohydrate chain in (I) has a zigzag conformation and the aromatic amine group has a transitional sp ²/sp ³ geometry. Bond lengths and valence angles in the carbohydrate portion compare well with the average values for related acyclic polyol structures. All of the hydroxyl groups are involved in inter­molecular hydrogen bonding and form a two-dimensional network of infinite chains, which are inter­linked by intra­molecular hydrogen bonds and organized into R ₈ ⁸(16) homodromic ring patterns. A comparative Hirshfeld surfaces analysis of (I) and four other 1-amino-1-de­oxy-d-fructose derivatives suggests the balance of hydro­philic/hydro­phobic inter­actions plays a role in the crystal packing, favoring the acyclic isomer.

Chemical context  

Reducing carbohydrates, for instance aldoses (glucose, mannose, xylose) or ketoses (fructose, ribulose), mutarotate in solutions such that the predominant species in equilibrium consist of cyclic pyran­ose and furan­ose hemiacetals or hemiketals, respectively (Angyal, 1992 ▸). Free aldehyde or ketone forms are thermodynamically unfavorable and normally comprise less than 1% of the population in the equilibria. Crystallization of reducing monosaccharides naturally affords the most populous, predominantly pyran­ose, anomers (Jeffrey, 1990 ▸). Previously, we have demonstrated that exceptions to this rule may be found among 1-amino-1-de­oxy-ketoses. Only four acyclic ketosamine structures have been accurately characterized by X-ray diffraction so far (Mossine et al., 1995 ▸, 2002 ▸, 2009 ▸); however, it was suggested that the hydro­phobic nature of the amino substituents may play a supporting role in stabilization of the unique structures (Mossine et al., 2009 ▸). Given that the concept of acyclic inter­mediates is essential for understanding the mechanisms of many enzymatic and non-enzymatic transformations of carbohydrates in general (see, for example, Buchholz & Seibel, 2008 ▸; Wang et al., 2014 ▸) and natural fructosamines in particular (Nursten, 2005 ▸), the availability of precise structural knowledge on the open-chain 1-amino-1-de­oxy-ketoses is of inter­est to the field. We report here on the structure of title compound, alternatively named as d-fructose-N-methyl-p-anisidine, C₁₄H₂₁NO₆, (I), aiming to expand this knowledge.

Structural commentary  

The mol­ecular structure and atomic numbering for (I) are shown in Fig. 1 ▸. The mol­ecule may be considered as a conjugate of a carbohydrate, 1-amino-1-de­oxy-d-fructose, and an aromatic amine, N-methyl-p-anisidine, which are joined through the common amino group. The carbohydrate portion in (I) exists in the acyclic keto form. Remarkably, in the aqueous solution of (I), the acyclic keto form is a minor constituent of the established equilibrium, at 10.3% of the total population as follows from the ¹³C NMR data (Table 1 ▸). The predominant β-pyran­ose anomer (52.0%) and smaller proportions of the β-furan­ose, α-pyran­ose, and α-furan­ose cyclic forms constitute the rest of the equilibrium composition (Fig. 2 ▸).

Figure 1.

Atomic numbering and displacement ellipsoids at the 50% probability level for (I). Intra­molecular O—H⋯O inter­actions are shown as dotted lines.

Table 1. Distribution (%) of cyclic and acyclic forms of some 1-amino-1-de­oxy-D-fructose derivatives in D₂O/pyridine (1:1) at 293 K, as estimated from the ¹³C NMR spectra, and in the crystalline state.

Compound	α-pyran­ose	β-pyran­ose	α-furan­ose	β-furan­ose	acyclic, keto	Crystalline isomers
(I)	2.1	52.0	4.9	30.6	10.3	acyclic keto
FruNMptia	2.1	49.9	4.8	32.2	11.0	acyclic keto
FruNEpcaa	2.0	48.7	4.2	32.3	12.7	acyclic keto
Fruptia,b	3.5	61.0	9.4	24.2	1.9	β-pyran­ose
FruAllac	2.2	47.4	4.5	33.6	12.3	β-pyran­ose
Fructosamined	5.0	70.8	11.2	12.3	0.8	β-pyran­ose
FruAibe	3.0	75.6	10.1	10.4	<0.7	β-pyran­ose

Notes: (a) Mossine et al. (2009 ▸); (b) Gomez de Anderez et al. (1996 ▸); (c) Mossine et al. (2009a ▸); (d) Mossine et al. (2009b ▸); (e) Mossine et al. (2018 ▸).

Figure 2.

Isomerization equilibrium of (I) in solution.

The carbohydrate fragment of the mol­ecule is in the zigzag conformation, having four out of six of its carbon atoms, C3, C4, C5, and C6, located in one plane. The conformation around the carbonyl group is also nearly flat and involves atoms N1, C1, C2, O2, C3, and O3, with the carbonyl O2 in the syn-periplanar position with respect to both N1 and O3 [respective torsion angles are 11.7 (3) and −7.0 (3)°]. This type of conformation is preferred for the β-amino­carbonyl group, due to influence of the σ_C—H → σ_C=O* and σ_C—H → π_C=O* hyperconjugation in conditions when inter­action between the nitro­gen lone pair (LP) and the carbonyl π*-system is not significant (Ducati et al., 2006 ▸). Indeed, the LP—N1—C1—C2 torsion angle estimate is close to 180° in (I). In the sugar portion of (I), the average C—O bond distances (1.43 ± 0.01Å) and the valence angles in hydroxyl groups are close to the average values for a number of crystalline alditol structures (Jeffrey & Kim, 1970 ▸) and acyclic ketosamines (Mossine et al., 1995 ▸, 2002 ▸, 2009 ▸). Two heteroatom contacts, O3—H⋯O4 and O6—H⋯O5, although weakly directional (Table 2 ▸), are cooperatively integrated into the hydrogen-bonding scheme (see Section 3) and thus are good candidates to qualify for intra­molecular hydrogen bonds. The tertiary amino group geometry is a flattened pyramid, with the distance from the N1 apex to the C1–C7–C13 base being 0.219 Å and the average base-face dihedral angle 17.2°. The N1—C7 distance, at 1.403 Å, is significantly shorter than the distances from N1 to the aliphatic carbons C1 and C13 [1.444 (3) and 1.455 (3) Å]. Such geometry is characteristic for amino groups with a mixed sp ³/sp ² hybridization, likely due to a partial resonance of the nitro­gen p-electrons with a neighboring π-system, such as the benzene ring in (I). In the solid-state ¹³C NMR spectrum (Fig. 3 ▸), the peaks corresponding to the carbons C1, C7, and C13 are split, indicating a conformational dimorphism of the tertiary amino group, possibly due to an inversion of configuration at the N1 atom.

Table 2. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3O⋯O4	0.87 (3)	2.67 (3)	2.962 (2)	101 (3)
O3—H3O⋯O5i	0.87 (3)	1.94 (3)	2.747 (2)	153 (2)
O4—H4O⋯O6ii	0.80 (3)	1.90 (3)	2.700 (2)	176 (3)
O5—H5O⋯O3iii	0.86 (3)	1.86 (3)	2.702 (2)	165 (3)
O6—H6O⋯O5	0.82 (3)	2.56 (3)	2.918 (2)	108 (3)
O6—H6O⋯O4iv	0.82 (3)	1.95 (3)	2.704 (2)	154 (3)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

Figure 3.

Solid-state ¹³C NMR spectrum of powdered crystalline (I).

Supra­molecular features  

Compound (I) crystallizes in the monoclinic space group P2₁, with two equivalent mol­ecules per unit cell. The mol­ecular packing of (I) features ‘hydro­philic’ and ‘hydro­phobic’ layers propagating in the ab plane (Fig. 4 ▸). The carbohydrate residues form a two-dimensional network of hydrogen bonds organized as a system of two homodromic infinite chains, with ⋯O3—H⋯O5—H⋯ and ⋯O4—H⋯O6—H⋯ recurrent sequences of inter­molecular hydrogen bonds. These chains are topologically connected by the intra­molecular short heteroatom contacts O3—H⋯O4 and O6—H⋯O5. Basic hydrogen-bonding patterns of the resulting network are depicted in Fig. 5 ▸ and include fused homodromic (16) and anti­dromic (4) rings (the pattern notation according to Bernstein et al., 1995 ▸). The inter­molecular heteroatom contacts that define the hydrogen bonding in (I) are not confined exclusively to the carbohydrate portion of the mol­ecule (Fig. 6 ▸), however. In addition, there are two close C—H⋯O2 contacts involving the carbonyl group, and two short C—H⋯π contacts between the methyl groups and the benzene ring centroids (Cg1), which may qualify as weak hydrogen bonds (Table 3 ▸, Fig. 6 ▸). The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009 ▸) revealed that a major proportion of the inter­molecular contacts in crystal structure of (I) is provided by non- or low-polar inter­actions of the H⋯H and C⋯H type (Fig. 7 ▸ and Table 4 ▸).

Figure 4.

The mol­ecular packing in (I). Color code for crystallographic axes: red – a, green – b, blue – c. Hydrogen bonds are shown as cyan dotted lines.

Figure 5.

Hydrogen-bonding pattern in the crystal structure of (I).

Figure 6.

Views of the Hirshfeld surface for (I) mapped over: (a) the electrostatic potential in the range −0.0966 to +0.1843 a.u. The red and blue colors represent the distribution of the negative and positive electrostatic potential, respectively; (b) the d _e function, in the range 0.683 to 2.484 Å, calculated for the external contact atoms in the crystal. Shown are mol­ecular fragments involved in the C—H⋯π inter­actions (black dotted lines) and the shortest H⋯H contact (red dotted line).

Table 3. Suspected C—H⋯A contacts (Å, °).

C—H⋯A	C—H	H⋯A	C⋯A	C—H⋯A	Symmetry
C1—H1A⋯O2	0.99	2.48	3.386 (3)	152	x, y − 1, z
C14—H14B⋯O2	0.98	2.52	3.311 (3)	138	-x + 1, y − , −z + 1
C14—H14A⋯Cg1	0.98	2.95	3.747 (3)	139	-x + 1, y − , −z + 1
C13—H13C⋯Cg1	0.98	2.80	3.539 (2)	133	-x, y + , −z + 1

Figure 7.

(a) The full two-dimensional fingerprint plot for (I) and those delineated for the specific contacts: (b) O⋯H; (c) H⋯H; (d) C⋯H.

Table 4. Contributions (%) of specific contact types to the Hirshfeld surfaces of 1-amino-1-de­oxy-D-fructose derivatives.

Compound	Conformation	O⋯H	H⋯H	C⋯H	Other contacts
(I)	acyclic keto	32.3	52.8	13.2	N⋯H 1.6; C⋯C 0.1
FruNMptia	acyclic keto	26.5	59.8	11.8	N⋯H 1.6; C⋯C 0.3
FruNEpcaa	acyclic keto	23.1	50.1	8.6	N⋯C 0.5; C⋯C 1.3; Cl⋯H 13.1; Cl⋯C 3.4
FruNAllab	β-pyran­ose	15.2	67.7	16.9	C⋯C 0.1
FruNBn2 c	β-pyran­ose	16.5	64.2	19.2	C⋯O 0.1
TagNMBnd	α-pyran­ose	20.6	65.8	13.5	O⋯O 0.1

Notes: (a) Mossine et al. (2009 ▸); (b) Mossine et al. (2009a ▸); (c) Hou et al. (2001 ▸); (d) Pérez et al. (1978 ▸).

Database survey  

A search of SciFinder, Google Scholar, and the Cambridge Structural Database (Groom et al., 2016 ▸) by both structure and chemical names for 1-de­oxy-1-(N-methyl-p-meth­oxy­phenyl­amino)-d-fructose returned no references; hence compound (I) is new. There are four closely related structures, namely d-fructose-N-methyl-p-toluidine (FruNMpti, CCDC 717802), d-fructose-p-toluidine (Frupti, CCDC 126260), d-fructose-N-ethyl-p-chloro­aniline (FruNEpca, CCDC 717803), and d-fructose-N-allyl­aniline (FruNAlla, CCDC 717417). Each of these 1-amino-1-de­oxy-d-fructose derivatives features an aromatic substituent at the amino group. They also display a similar to (I) distribution of the cyclic and acyclic tautomeric forms in solutions (Table 1 ▸). However, only FruNMpti and FruNEpca were reported to adopt the acyclic keto conformations in crystalline state. Frupti (Gomez de Anderez et al., 1996 ▸), FruNAlla (Mossine et al., 2009a ▸), as well as the rest of the 1-amino-1-de­oxy-d-fructose derivatives whose structures were solved by X-ray diffraction methods (about 15 structures so far), crystallize in the β-d-fructo­pyran­ose anomeric form (Table 1 ▸). The unusual propensity of some 1-amino-1-de­oxy-d-fructose derivatives, including (I), to crystallize in a thermo­dynamically unfavored acyclic form is difficult to explain, given that the number of the available solved structures is thus far too small. Modelling the energies of inter­molecular inter­actions experienced by these mol­ecules in solutions versus crystal environments was beyond the goals of the current study. However, some initial clues can be derived from analysis of data compiled in Table 1 ▸, this work, as well as in Table 1 ▸ from our previous study (Mossine et al., 2009 ▸). First, only fructosamine derivatives decorated with an aromatic amino substituent can, but not always, crystallize as the acyclic keto tautomer. As pointed out in Section 2, a neighboring π-system may resonate with the amine p-electrons thus making them unavailable for σ-bonding. Next, among N-aryl derivatives of 1-amino-1-de­oxy-d-fructose, only those lacking a proton bound to the tertiary amino group can crystallize in the acyclic form. Indeed, no hydrogen bonds involving N1 were detected in acyclic (I), FruNMpti or FruNEpca (Mossine et al., 2009 ▸). In contrast, the structures of Frupti, FruAlla and all the rest of the 1-amino-1-de­oxy-d-fructose derivatives reveal at least one hydrogen-mediated intra­molecular heteroatom contact between the amino nitro­gen atom and an oxygen atom originating from the carbohydrate portion of the mol­ecule, most often the anomeric O2. Thus, the inability of the amino group to form stable intra­molecular hydrogen bonds with the carbohydrate portion plays a role in stabilization of the acyclic tautomer. Finally, a comparative Hirshfeld surfaces analysis (Table 4 ▸) of these structures suggests that the extended linear conformation of the acyclic tautomer may require more of the ‘hydro­philic space’ available in the crystal structure, as compared to the pyran­ose anomers. This argument also seems to be supported by an observation that an increase in size of the N-substituents, such as from methyl or ethyl (in FruNMpti and FruNEpca) to allyl or butyl (in FruAlla and d-fructose-N-butyl­aniline), leads to a loss of propensity to crystallize in the acyclic form (Mossine et al., 2009 ▸).

Synthesis and crystallization  

The preparation of (I) was performed following a protocol described previously (Mossine et al., 2009 ▸). Briefly, a mixture of 5.4 g (0.03 moles) of d-glucose, 2.7 g (0.022 moles) of p-anisidine and 0.55 mL of 3-mercaptopropionic acid catalyst/anti­oxidant was stirred for 6 h in 12 mL of iso­propanol in a screw-capped glass vial at 360 K. The reaction progress was followed by TLC. The purification step included an ion-exchange on Amberlite IRN-77 (H⁺), with 0.2 M NH₄OH in 50% ethanol as an eluant, and was followed by flash filtration on a short silica column using 5% MeOH in CH₂Cl₂ as an eluant. Crystallization of the compound was aided by the addition of a small amount of acetone to the syrupy evaporation residue. The crystals were filtered off, washed with acetone and dried in vacuo over CaCl₂, yield 1.6 g (27%, based on starting amine) of colorless prisms. Major (β-pyran­­ose anomer) peaks (ppm) in the ¹³C NMR spectrum in D₂O/pyridine: 154.14 (C10); 148.12 (C7); 117.86, 117.11 (C8, C12); 116.96, 116.80 (C9, C11); 101.56 (C2); 72.98 (C4); 71.99 (C3, C5); 65.90 (C6); 63.21 (C1); 57.84 (C14); 42.62 (C13). The ¹³C CPMAS–TOSS spectrum of finely powdered crystalline (I) is shown in Fig. 3 ▸ and the minor peak assignments are listed in Supplementary Table S1.

Refinement  

Crystal data, data collection and structure refinement details are summarized in Table 5 ▸. Hy­droxy and nitro­gen-bound H atoms were located in difference-Fourier analyses and were allowed to refine fully. Other H atoms were placed at calculated positions and treated as riding, with C—H = 0.98 Å (meth­yl), 0.99 Å (methyl­ene) or 1.00 Å (methine) and with U _iso(H) = 1.2U _eq(methine or methyl­ene) or 1.5U _eq(meth­yl). The Flack absolute structure parameter determined [0.3 (5) for 1149 quotients (Parsons et al., 2013 ▸)] is consistent with the (3S,4R,5R) configuration which was assigned for this chain system on the basis of the known configuration for the starting material d-glucose (McNaught, 1996 ▸).

Table 5. Experimental details.

Crystal data
Chemical formula	C14H21NO6
M r	299.32
Crystal system, space group	Monoclinic, P21
Temperature (K)	100
a, b, c (Å)	10.8002 (15), 5.1439 (7), 13.3931 (19)
β (°)	98.382 (1)
V (Å3)	736.11 (18)
Z	2
Radiation type	Mo Kα
μ (mm−1)	0.11
Crystal size (mm)	0.35 × 0.15 × 0.12
Data collection
Diffractometer	Bruker APEXII CCD area detector
Absorption correction	Multi-scan (SADABS; Sheldrick (2003 ▸)
T min, T max	0.88, 0.99
No. of measured, independent and observed [I > 2σ(I)] reflections	8031, 2993, 2788
R int	0.026
(sin θ/λ)max (Å−1)	0.625
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.031, 0.082, 1.04
No. of reflections	2993
No. of parameters	208
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.19, −0.15
Absolute structure	Flack x determined using 1149 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸)
Absolute structure parameter	0.3 (5)

Computer programs: SMART and SAINT (Bruker, 1998 ▸), SHELXS97 (Sheldrick, 2008 ▸), SHELXL2017/1 (Sheldrick, 2015 ▸), X-SEED (Barbour, 2001 ▸), Mercury (Macrae et al., 2008 ▸), CIFTAB (Sheldrick, 2008 ▸) and publCIF (Westrip, 2010 ▸).

Supplementary Material

CCDC reference: 1811885

Additional supporting information: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Crystal data

C14H21NO6	F(000) = 320
Mr = 299.32	Dx = 1.350 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 10.8002 (15) Å	Cell parameters from 3774 reflections
b = 5.1439 (7) Å	θ = 2.6–25.8°
c = 13.3931 (19) Å	µ = 0.11 mm−1
β = 98.382 (1)°	T = 100 K
V = 736.11 (18) Å3	Prism, colourless
Z = 2	0.35 × 0.15 × 0.12 mm

Data collection

Bruker APEXII CCD area detector diffractometer	2788 reflections with I > 2σ(I)
ω scans	Rint = 0.026
Absorption correction: multi-scan (SADABS; Sheldrick (2003)	θmax = 26.4°, θmin = 1.9°
Tmin = 0.88, Tmax = 0.99	h = −13→13
8031 measured reflections	k = −6→6
2993 independent reflections	l = −16→16

Refinement

Refinement on F2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.031	w = 1/[σ2(Fo2) + (0.0443P)2 + 0.0803P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.082	(Δ/σ)max < 0.001
S = 1.04	Δρmax = 0.19 e Å−3
2993 reflections	Δρmin = −0.15 e Å−3
208 parameters	Absolute structure: Flack x determined using 1149 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: 0.3 (5)

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
N1	0.10655 (16)	0.5973 (4)	0.64477 (12)	0.0275 (4)
C1	0.15040 (19)	0.4862 (4)	0.74257 (15)	0.0267 (4)
H1A	0.189953	0.316322	0.732685	0.032*
H1B	0.077318	0.453299	0.777617	0.032*
O2	0.26415 (14)	0.8787 (3)	0.79127 (12)	0.0321 (4)
C2	0.24391 (18)	0.6543 (4)	0.81040 (15)	0.0240 (4)
O3	0.40317 (13)	0.6914 (3)	0.95778 (11)	0.0268 (3)
C3	0.31015 (18)	0.5253 (4)	0.90646 (15)	0.0229 (4)
H3	0.352434	0.364549	0.886440	0.027*
O4	0.13795 (14)	0.6653 (3)	0.99012 (12)	0.0281 (3)
C4	0.21360 (18)	0.4440 (4)	0.97432 (14)	0.0220 (4)
H4	0.159267	0.302656	0.940569	0.026*
O5	0.35348 (13)	0.1285 (3)	1.06292 (11)	0.0270 (3)
C5	0.27762 (17)	0.3493 (4)	1.07730 (15)	0.0231 (4)
H5	0.332604	0.491086	1.109907	0.028*
O6	0.09673 (13)	0.0803 (3)	1.10474 (11)	0.0285 (3)
C6	0.18494 (19)	0.2727 (5)	1.14715 (15)	0.0285 (5)
H6A	0.231641	0.204885	1.210924	0.034*
H6B	0.138815	0.429609	1.163615	0.034*
C7	0.18576 (18)	0.5977 (4)	0.57050 (15)	0.0250 (4)
C8	0.2825 (2)	0.4181 (5)	0.57062 (16)	0.0322 (5)
H8	0.300894	0.301939	0.625936	0.039*
C9	0.3529 (2)	0.4053 (5)	0.49151 (17)	0.0352 (5)
H9	0.417860	0.280262	0.493123	0.042*
O10	0.39239 (16)	0.5762 (4)	0.32846 (12)	0.0437 (4)
C10	0.3286 (2)	0.5736 (5)	0.41076 (16)	0.0319 (5)
C11	0.2348 (2)	0.7560 (5)	0.41043 (17)	0.0352 (5)
H11	0.218288	0.874400	0.355652	0.042*
C12	0.1644 (2)	0.7690 (5)	0.48871 (16)	0.0316 (5)
H12	0.100474	0.896471	0.486890	0.038*
C13	0.0158 (2)	0.8065 (5)	0.64424 (17)	0.0330 (5)
H13A	0.059076	0.974339	0.646201	0.050*
H13B	−0.027328	0.790523	0.703438	0.050*
H13C	−0.045390	0.795655	0.582714	0.050*
C14	0.4858 (2)	0.3812 (7)	0.3254 (2)	0.0474 (7)
H14A	0.551236	0.401318	0.383834	0.071*
H14B	0.522812	0.399739	0.263176	0.071*
H14C	0.447653	0.208769	0.327161	0.071*
H5O	0.430 (3)	0.175 (7)	1.061 (2)	0.050 (8)*
H4O	0.069 (3)	0.643 (7)	0.959 (2)	0.052 (9)*
H6O	0.133 (3)	−0.034 (6)	1.078 (2)	0.047 (8)*
H3O	0.368 (2)	0.835 (6)	0.974 (2)	0.041 (8)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
N1	0.0270 (9)	0.0286 (9)	0.0267 (9)	0.0036 (8)	0.0032 (7)	0.0003 (7)
C1	0.0277 (11)	0.0254 (10)	0.0268 (10)	−0.0020 (9)	0.0032 (8)	0.0011 (8)
O2	0.0344 (8)	0.0240 (8)	0.0372 (9)	−0.0023 (7)	0.0026 (7)	0.0027 (7)
C2	0.0207 (9)	0.0242 (10)	0.0288 (10)	0.0003 (8)	0.0099 (8)	−0.0007 (8)
O3	0.0166 (7)	0.0272 (8)	0.0365 (8)	−0.0027 (6)	0.0038 (6)	−0.0025 (6)
C3	0.0180 (9)	0.0223 (10)	0.0287 (10)	−0.0003 (7)	0.0048 (8)	−0.0013 (8)
O4	0.0178 (7)	0.0281 (8)	0.0383 (8)	0.0029 (6)	0.0040 (6)	−0.0057 (6)
C4	0.0172 (9)	0.0220 (10)	0.0274 (10)	0.0011 (7)	0.0052 (8)	−0.0023 (8)
O5	0.0168 (7)	0.0276 (8)	0.0368 (8)	0.0007 (6)	0.0045 (6)	0.0031 (6)
C5	0.0164 (9)	0.0270 (10)	0.0261 (10)	−0.0009 (8)	0.0037 (8)	−0.0033 (8)
O6	0.0190 (7)	0.0306 (8)	0.0370 (8)	−0.0016 (6)	0.0081 (6)	−0.0033 (7)
C6	0.0229 (10)	0.0363 (12)	0.0266 (10)	−0.0059 (9)	0.0043 (8)	−0.0020 (10)
C7	0.0244 (9)	0.0235 (10)	0.0258 (10)	−0.0023 (8)	−0.0012 (8)	−0.0044 (8)
C8	0.0327 (11)	0.0344 (12)	0.0288 (11)	0.0070 (10)	0.0021 (9)	0.0038 (9)
C9	0.0313 (11)	0.0390 (14)	0.0353 (12)	0.0084 (10)	0.0054 (9)	−0.0012 (10)
O10	0.0399 (9)	0.0585 (11)	0.0354 (9)	0.0012 (9)	0.0143 (7)	−0.0009 (8)
C10	0.0281 (11)	0.0398 (13)	0.0283 (10)	−0.0043 (10)	0.0055 (8)	−0.0046 (10)
C11	0.0376 (13)	0.0344 (12)	0.0335 (12)	0.0000 (10)	0.0054 (10)	0.0080 (10)
C12	0.0326 (11)	0.0263 (11)	0.0355 (12)	0.0058 (9)	0.0033 (9)	0.0040 (10)
C13	0.0294 (11)	0.0350 (13)	0.0346 (11)	0.0058 (10)	0.0044 (9)	−0.0031 (10)
C14	0.0331 (12)	0.0692 (19)	0.0416 (14)	0.0003 (13)	0.0115 (10)	−0.0126 (13)

Geometric parameters (Å, º)

N1—C7	1.403 (3)	O6—H6O	0.82 (3)
N1—C1	1.444 (3)	C6—H6A	0.9900
N1—C13	1.455 (3)	C6—H6B	0.9900
C1—C2	1.525 (3)	C7—C8	1.395 (3)
C1—H1A	0.9900	C7—C12	1.399 (3)
C1—H1B	0.9900	C8—C9	1.392 (3)
O2—C2	1.209 (3)	C8—H8	0.9500
C2—C3	1.529 (3)	C9—C10	1.380 (3)
O3—C3	1.418 (2)	C9—H9	0.9500
O3—H3O	0.87 (3)	O10—C10	1.382 (3)
C3—C4	1.538 (3)	O10—C14	1.428 (3)
C3—H3	1.0000	C10—C11	1.381 (3)
O4—C4	1.435 (2)	C11—C12	1.383 (3)
O4—H4O	0.80 (3)	C11—H11	0.9500
C4—C5	1.530 (3)	C12—H12	0.9500
C4—H4	1.0000	C13—H13A	0.9800
O5—C5	1.430 (2)	C13—H13B	0.9800
O5—H5O	0.86 (3)	C13—H13C	0.9800
C5—C6	1.518 (3)	C14—H14A	0.9800
C5—H5	1.0000	C14—H14B	0.9800
O6—C6	1.432 (3)	C14—H14C	0.9800
C7—N1—C1	119.35 (16)	C5—C6—H6A	108.9
C7—N1—C13	118.38 (17)	O6—C6—H6B	108.9
C1—N1—C13	115.40 (17)	C5—C6—H6B	108.9
N1—C1—C2	114.64 (18)	H6A—C6—H6B	107.7
N1—C1—H1A	108.6	C8—C7—C12	117.14 (18)
C2—C1—H1A	108.6	C8—C7—N1	122.18 (19)
N1—C1—H1B	108.6	C12—C7—N1	120.53 (19)
C2—C1—H1B	108.6	C9—C8—C7	121.5 (2)
H1A—C1—H1B	107.6	C9—C8—H8	119.3
O2—C2—C1	122.7 (2)	C7—C8—H8	119.3
O2—C2—C3	121.04 (19)	C10—C9—C8	120.3 (2)
C1—C2—C3	116.29 (17)	C10—C9—H9	119.9
C3—O3—H3O	109.2 (18)	C8—C9—H9	119.9
O3—C3—C2	110.97 (16)	C10—O10—C14	116.9 (2)
O3—C3—C4	111.77 (16)	C9—C10—C11	118.96 (19)
C2—C3—C4	109.93 (15)	C9—C10—O10	124.8 (2)
O3—C3—H3	108.0	C11—C10—O10	116.2 (2)
C2—C3—H3	108.0	C10—C11—C12	121.0 (2)
C4—C3—H3	108.0	C10—C11—H11	119.5
C4—O4—H4O	108 (2)	C12—C11—H11	119.5
O4—C4—C5	108.19 (15)	C11—C12—C7	121.1 (2)
O4—C4—C3	108.74 (16)	C11—C12—H12	119.4
C5—C4—C3	111.30 (15)	C7—C12—H12	119.4
O4—C4—H4	109.5	N1—C13—H13A	109.5
C5—C4—H4	109.5	N1—C13—H13B	109.5
C3—C4—H4	109.5	H13A—C13—H13B	109.5
C5—O5—H5O	111 (2)	N1—C13—H13C	109.5
O5—C5—C6	108.62 (17)	H13A—C13—H13C	109.5
O5—C5—C4	108.92 (15)	H13B—C13—H13C	109.5
C6—C5—C4	112.72 (16)	O10—C14—H14A	109.5
O5—C5—H5	108.8	O10—C14—H14B	109.5
C6—C5—H5	108.8	H14A—C14—H14B	109.5
C4—C5—H5	108.8	O10—C14—H14C	109.5
C6—O6—H6O	110 (2)	H14A—C14—H14C	109.5
O6—C6—C5	113.26 (17)	H14B—C14—H14C	109.5
O6—C6—H6A	108.9
C7—N1—C1—C2	75.2 (2)	C4—C5—C6—O6	55.7 (2)
C13—N1—C1—C2	−75.3 (2)	C1—N1—C7—C8	24.6 (3)
N1—C1—C2—O2	11.7 (3)	C13—N1—C7—C8	174.25 (19)
N1—C1—C2—C3	−169.53 (16)	C1—N1—C7—C12	−160.0 (2)
O2—C2—C3—O3	−7.0 (3)	C13—N1—C7—C12	−10.3 (3)
C1—C2—C3—O3	174.20 (16)	C12—C7—C8—C9	−1.6 (3)
O2—C2—C3—C4	117.2 (2)	N1—C7—C8—C9	174.0 (2)
C1—C2—C3—C4	−61.6 (2)	C7—C8—C9—C10	0.5 (4)
O3—C3—C4—O4	70.7 (2)	C8—C9—C10—C11	0.8 (4)
C2—C3—C4—O4	−53.0 (2)	C8—C9—C10—O10	−179.7 (2)
O3—C3—C4—C5	−48.3 (2)	C14—O10—C10—C9	3.2 (3)
C2—C3—C4—C5	−172.04 (16)	C14—O10—C10—C11	−177.2 (2)
O4—C4—C5—O5	180.00 (15)	C9—C10—C11—C12	−1.0 (4)
C3—C4—C5—O5	−60.6 (2)	O10—C10—C11—C12	179.5 (2)
O4—C4—C5—C6	59.4 (2)	C10—C11—C12—C7	−0.1 (4)
C3—C4—C5—C6	178.77 (18)	C8—C7—C12—C11	1.4 (3)
O5—C5—C6—O6	−65.1 (2)	N1—C7—C12—C11	−174.2 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3O···O4	0.87 (3)	2.67 (3)	2.962 (2)	101 (3)
O3—H3O···O5i	0.87 (3)	1.94 (3)	2.747 (2)	153 (2)
O4—H4O···O6ii	0.80 (3)	1.90 (3)	2.700 (2)	176 (3)
O5—H5O···O3iii	0.86 (3)	1.86 (3)	2.702 (2)	165 (3)
O6—H6O···O5	0.82 (3)	2.56 (3)	2.918 (2)	108 (3)
O6—H6O···O4iv	0.82 (3)	1.95 (3)	2.704 (2)	154 (3)

Symmetry codes: (i) x, y+1, z; (ii) −x, y+1/2, −z+2; (iii) −x+1, y−1/2, −z+2; (iv) x, y−1, z.

Supplementary Table S1. Chemical shifts (ppm) of peaks for selected carbon atoms in a ¹³C NMR spectrum of (I) in D₂O/pyridine (1:1) at 293 K and in the solid state

Carbon	α-pyranose	β-pyranose	α-furanose	β-furanose	acyclic keto	solid state
C1	60.97	63.21	61.28	61.28	62.41	57.23
C2	101.13	101.56	108.26	105.62	215.08	210.04
C3	73.62	71.99	84.62	79.73	78.93	77.80
C4	74.92	72.98	80.26	77.42	74.96	69.59
C5	66.66	71.99	85.64	83.77	73.45	69.59
C6	63.7	65.90	64.37	65.14	65.81	64.70
C13	n.r.	42.62	n.r.	42.09	41.85	39.56

Funding Statement

This work was funded by University of Missouri Agriculture Experiment Station Chemical Laboratories grant .